Biomarker panels, diagnostic methods and test kits for ovarian cancer

Abstract

Methods are provided for predicting the presence, subtype and stage of ovarian cancer, as well as for assessing the therapeutic efficacy of a cancer treatment and determining whether a subject potentially is developing cancer. Associated test kits, computer and analytical systems as well as software and diagnostic models are also provided.

1 . A method of determining the ovarian cancer status of a subject, comprising the steps of:
 measuring the level of CA-125, HE4 and one or more biomarkers selected from the group consisting of IL-2 receptor alpha (IL-2Ra), Alpha-1-Antitrypsin (AAT), C-Reactive Protein (CRP), YKL-40, Cellular Fibronectin (cFib), prostasin, Tissue Inhibitor of Metalloproteinases 1 (TIMP-1), IL-8, IL-6, Vascular Endothelial Growth Factor B (VEGF-B), Matrix Metalloproteinase-7 (MMP-7), calprotectin, Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Lectin-Like Oxidized LDL Receptor 1 (LOX-1), neuropilin-1, TNFR2, and MPIF-1 in a biological sample obtained from the subject; and   correlating the measurements with ovarian cancer status.   
     
     
         2 . The method of  claim 1 , further comprising measuring the level of Cancer Antigen 72-4 (CA-72-4). 
     
     
         3 . The method of  claim 1 , wherein the ovarian cancer status is the presence, absence, or risk of ovarian cancer. 
     
     
         4 . The method of  claim 1  further comprising:
 managing subject treatment based on the status. 
 
     
     
         5 . The method of  claim 4 , wherein managing subject treatment is selected from the group consisting of ordering more tests, performing surgery, and taking no further action. 
     
     
         6 . The method of  claim 4  further comprising:
 measuring the level of said biomarkers after subject management; 
 correlating the measurements with ovarian cancer status; and 
 determining if subject management resulted in a change in ovarian cancer status. 
 
     
     
         7 . The method of  claim 1 , wherein measuring is selected from detecting the presence or absence of the biomarkers, quantifying the amount of biomarkers, and qualifying the type of biomarker. 
     
     
         8 . The method of  claim 1 , wherein the biomarkers are measured by an immunoassay and mass spectroscopy. 
     
     
         9 . The method of  claim 1 , wherein the correlating is performed by a software classification algorithm. 
     
     
         10 . The method of  claim 1 , wherein the sample is selected from blood, serum, and plasma. 
     
     
         11 . A kit comprising:
 a) a panel of affinity reagents that each selectively binds to CA-125, HE4 and one or more biomarkers selected from the group consisting of Interleukin-2 receptor alpha (IL-2 receptor alpha), Alpha-1-Antitrypsin (A AT), C-Reactive Protein (CRP), YKL-40, Cellular Fibronectin (cFib), Cancer Antigen 72-4 (CA-72-4), prostasin, Tissue Inhibitor of Metalloproteinases 1 (TIMP-1), IL-8, Matrix Metalloproteinase-7 (MMP-7), IL-6, Vascular Endothelial Growth Factor B (VEGF-B), calprotectin, Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Lectin-Like Oxidized LDL Receptor 1 (LOX-1), neuropilin-1, TNFR2, and MPIF-1; and   b) instructions for the use of said panel in the method of  claim 1 .   
     
     
         12 . The kit of  claim 11 , wherein the affinity reagent is an antibody. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . A panel of biomarkers comprising CA-125, HE4, and one or more biomarkers selected from the group consisting of Interleukin-2 receptor alpha (IL-2 receptor alpha), Alpha-1-Antitrypsin (A AT), C-Reactive Protein (CRP), YKL-40, Cellular Fibronectin (cFib), Cancer Antigen 72-4 (CA-72-4), prostasin, Tissue Inhibitor of Metalloproteinases 1 (TIMP-1), IL-8, Matrix Metalloproteinase-7 (MMP-7), IL-6, Vascular Endothelial Growth Factor B (VEGF-B), calprotectin, Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Lectin-Like Oxidized LDL Receptor 1 (LOX-1), neuropilin-1, TNFR2, and MPIF-1. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the subject is a postmenopausal subject, and the biomarkers measured are CA-125, HE4 and IL2-Ralpha. 
     
     
         18 . The method of  claim 1 , wherein the subject has early stage ovarian cancer, and the biomarkers measured are HE4, CA 125, and CRP or CA-72-4.